Medical Science, BioPharmaceuticals TA, R&D, AstraZeneca K.K., Tokyo, Japan.
Clinical Science, BioPharmaceuticals TA, R&D, AstraZeneca K.K., Tokyo, Japan.
Diabetes Obes Metab. 2023 Aug;25(8):2290-2299. doi: 10.1111/dom.15107. Epub 2023 Jun 19.
To assess the safety/tolerability, efficacy and pharmacokinetics of once-daily, 600-μg cotadutide in Japanese type 2 diabetes patients with a body mass index of 25 kg/m or higher.
This phase I, randomized, double-blind, placebo-controlled study (NCT04208620) enrolled patients to receive subcutaneous cotadutide at an escalating dose to determine the highest tolerated clinical dose (Cohort 1), then applied in Cohort 2. The primary endpoint was safety, including treatment-emergent adverse events (TEAEs); secondary endpoints included glycaemic control and body weight.
Sixteen patients were randomly allocated to receive cotadutide or placebo in a 3:1 ratio. All patients were Asian, 62.5% were male, and the median age and body mass index were 60 years and 27.2 kg/m , respectively. Through the follow-up period of the study, 11/12 (91.7%) patients in the cotadutide group experienced a TEAE versus 1/4 (25.0%) patients in the placebo group. All TEAEs were mild, except for one moderate event. There were no deaths, serious TEAEs or TEAEs leading to study discontinuation. Gastrointestinal-related events were the most common TEAEs. Cotadutide-treated patients achieved significantly improved 7-day mean glucose measured by continuous glucose monitoring; the 7-day mean (standard deviation) at the end of treatment (day 70) was 112.23 (20.79) versus 206.85 (3.62) mg/dL for placebo. Mean respective changes in HbA1c were -1.13% (0.64%) and -0.17% (0.65%); and mean percentage changes in body weight were -6.93% (3.44%) and -1.23% (1.20%).
Cotadutide was well tolerated at doses up to 600 μg; efficacy versus placebo for weight loss and glycaemic control was shown.
评估每日一次、600μg 剂量的科特杜肽在体重指数（BMI）为 25kg/m 或更高的日本 2 型糖尿病患者中的安全性/耐受性、疗效和药代动力学。
这是一项 I 期、随机、双盲、安慰剂对照研究（NCT04208620），纳入患者接受皮下注射科特杜肽，以确定最高耐受临床剂量（Cohort 1），然后在 Cohort 2 中应用。主要终点为安全性，包括治疗期不良事件（TEAE）；次要终点包括血糖控制和体重。
16 名患者按 3:1 的比例随机分配接受科特杜肽或安慰剂治疗。所有患者均为亚洲人，62.5%为男性，中位年龄和 BMI 分别为 60 岁和 27.2kg/m。在研究随访期间，科特杜肽组 12/12（91.7%）名患者发生 TEAE，安慰剂组 1/4（25.0%）名患者发生 TEAE。所有 TEAE 均为轻度，除 1 例中度事件外。无死亡、严重 TEAE 或因 TEAE 导致研究中止。胃肠道相关事件是最常见的 TEAE。科特杜肽治疗组患者的连续血糖监测 7 天平均血糖显著改善；治疗结束时（第 70 天）7 天平均（标准差）为 112.23（20.79）mg/dL，安慰剂组为 206.85（3.62）mg/dL。分别HbA1c 的平均变化为-1.13%（0.64%）和-0.17%（0.65%）；体重的平均百分比变化为-6.93%（3.44%）和-1.23%（1.20%）。
科特杜肽在高达 600μg 的剂量下耐受良好；与安慰剂相比，在体重减轻和血糖控制方面具有疗效。
